Regeneration and maturation of periodontal tissues following implantation of rhGDF-5/ß-TCP in one-wall intrabony defects in dogs

Abstract

Purpose: Recombinant human growth/differentiation factor-5 (rhGDF-5) is being evaluated as a candidate therapy in support of periodontal regeneration. The objectives of this study were 1) to evaluate effects of rhGDF-5 in a particulate ß-TCP carrier on periodontal regeneration at 8 weeks observational period, and 2) to charaterize their maturation process of regenerated periodontal tissues by rhGDF-5 using an established periodontal defect model and a 24-week healing interval.Materials and Methods: Unilateral, 4 x 4 x 5 mm (length x width x height), one-wall, critical-size, intrabony periodontal defects were surgically created at the mandibular 2nd and 4th premolar teeth, and the defects were treated by experimental protocols in twenty among total twenty-four young adult Beagle dogs; fifteen animals were used for effectiveness evaluation using 8 weeks healing period, and the other five animals for long-term safety evaluation using 24 weeks healing interval. Eight-week-observation study included three groups; sites received rhGDF-5/β-TCP (n=5), ß-TCP solo (n=5), and sham-surgery control (n=5). Twenty-four-week-observation study also included two groups; sites received rhGDF-5/β-TCP (n=5), and pristine control (n=4). Bilateral sites at the 4th premolar in dogs of pristine control group received mucogingival flap surgery without defect induction. Histologic slides of rhGDF-5/β-TCP group from the 8-week-observation study were used to compare tissue maturation between 8 and 24 weeks.Results: Sites implanted with rhGDF-5/ß-TCP exhibited significantly enhanced cementum and bone formation compared to ß-TCP and sham-surgery controls in 8-week-observation study. Controls exhibited mostly woven bone with primary osteons, whereas rhGDF-5/ß-TCP sites showed a noticeable extent of lamellar bone. Sites receiving rhGDF-5/ß-TCP or ß-TCP showed some residual ß-TCP granules apparently undergoing biodegradation without obvious differences between the sites. Linear histometric observations of cementum and alveolar regeneration showed no significant differences between the 8- and 24-week observation intervals in sites received rhGDF-5/ß-TCP. However, parameters of periodontal tissue maturation showed significant differences between the observation intervals including increased fraction mineralized tissue and lamellar bone (p<0.05) and decreased osteocyte counts (p<0.05) at 24 compared with 8 weeks. Conclusions: RhGDF-5/ß-TCP has a greater potential to support regeneration of the periodontal attachment, and regenerated periodontal tissues in sites receiving rhGDF-5/ß-TCP may undergo progressive maturation without debilitating aberrant tissue reactions.